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Metastasis is an important cause of cancer-related death. Previous studies in our laboratory found that pregnane alkaloids from Pachysandra terminalis had antimetastatic activity against breast cancer cells. In the current study, we demonstrated that treatment with one of the alkaloid derivatives, (Z)-3β-ethylamino-pregn-17(20)-en (1), led to the downregulation of the HIF-1α/VEGF/VEGFR2 pathway, suppressed the phosphorylation of downstream molecules Akt, mTOR, FAK, and inhibited breast cancer metastasis and angiogenesis both in vitro and in vivo. Furthermore, the antimetastasis and antiangiogenesis effects of 1 treatment (40 mg/kg) were more effective than that of Sorafenib (50 mg/kg). Surface plasmon resonance (SPR) analysis was performed and the result suggested that HSP90α was a direct target of 1. Taken together, our results suggested that compound 1 might represent a candidate antitumor agent for metastatic breast cancer.

Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy.Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis.Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis.Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

A novel triterpene, 2α,3β,20,23-tetrahydroxyurs-28-oic acid (1), was isolated from the aerial part of Centella asiatica. Its structure was elucidated by spectroscopic methods, including 2D-NMR spectra. It displayed no activity against Hela and A549 cell lines at concentrations of 10 and 30 μg/mL, respectively.

Nine new pregnane alkaloids (1–9), together with eight known alkaloids (10–17), were isolated from the whole herb of Pachysandra terminalis. Their structures were elucidated on the basis of spectroscopic analyses. In addition, the isolates were examined for their ability to inhibit the migration of MDA-MB-231 cells induced by the chemokine epidermal growth factor (EGF). Alkaloids 1, 5, 7, 9, 12, and 17 presented significant anti-metastasis activities compared with the positive reagent, LY294002.

The title compound, C29H37NO2, crystallized with two independent molecules in an asymmetric unit in which the conformation of the cyclohexyl ring of the pregnene moiety bonded to the 3α-(1,3-dioxoisoindolin-2-yl)- ring system differs: in one molecule it is in a chair conformation, while in the other it exhibits a half-chair conformation. The other six-membered rings in the pregnene moiety are in chair conformations and the five-membered rings are in envelope forms in both molecules. In both molecules, the 3α-(1,3-dioxoisoindolin-2-yl)- ring systems are individually approximately planar, with r.m.s. devtaions 0.0148 and 0.0264 Å. The structure is consolidated by intermolecular C—H...O hydrogen-bonding interactions involving the carbonyl O atoms and methyl, methylene and methylidyne groups, resulting in a two-dimensional structure.

The title compound, C14H24NO+·Cl−, crystallizes with four independent molecules in the asymmetric unit. It was isolated from plant Pachysandra terminalis Siebold & Zucc. The six-membered ring has a conformation close to an envelope. In the crystal, N—H...Cl hydrogen-bonding interactions exist between secondary ammonium groups and free chloride anions, resulting in a one-dimensional supramolecular structure oriented along [100]. The crystal studied was found to be a two-component non-merohedral twin with twin law [-100/0-10/101], the fractional contribution of the minor component being approximately 33%.

The title compound, C18H28O4, crystallizes with two molecules in the asymmetric unit. Both molecules have similar conformations of nine-membered rings, which are trans-fused with cyclobutane fragments. The puckering amplitudes (q2) of the cyclobutane rings are 0.2451 (2) and 0.2526 (2) Å.

In the title compound, C16H15N3O, the triazole ring makes dihedral angles of 7.08 (2) and 74.53 (3)° with the two outer aromatic rings. The crystal packing is stabilized by very short intermolecular C—H...O hydrogen bonds and weak π–π stacking interactions [centroid-to-centroid distance 3.632 (3) Å], resulting in the formation of zigzag chains parallel to the b axis.

Nine new pregnane alkaloids (1-9), together with eight known alkaloids (10-17), were isolated from the whole herb of Pachysandra terminalis. Their structures were elucidated on the basis of spectroscopic analyses. In addition, the isolates were examined for their ability to inhibit the migration of MDA-MB-231 cells induced by the chemokine epidermal growth factor (EGF). Alkaloids 1, 5, 7, 9, 12, and 17 presented significant anti-metastasis activities compared with the positive reagent, LY294002. [ABSTRACT FROM AUTHOR]

Tumor metastasis is the main cause of lethality of prostate cancer, because conventional therapies like surgery and hormone treatment rarely work at this stage. Tumor cell migration, invasion and adhesion are necessary processes for metastasis. By providing nutrition and an escape route from the primary site, angiogenesis is also required for tumor metastasis. Phosphatidylinositol 3-kinases (PI3Ks) are well known to play important roles in tumorigenesis as well as metastasis. ZSTK474 is a specific PI3K inhibitor developed for solid tumor therapy. In the present report, antimetastatic activities of ZSTK474 were investigated in vitro by determining the effects on the main metastatic processes. ZSTK474 exhibited inhibitory effects on migration, invasion and adhesive ability of prostate cancer PC3 cells. Furthermore, ZSTK474 inhibited phosphorylation of Akt substrate-Girdin, and the secretion of matrix metalloproteinase (MMP), both of which were reported to be closely involved in migration and invasion. On the other hand, ZSTK474 inhibited the expression of HIF-1a and the secretion of vascular endothelial growth factor (VEGF), suggesting its potential antiangiogenic activity on PC3 cells. Moreover, we demonstrated the antiangiogenesis by determining the effect of ZSTK474-reduced VEGF on tube formation of human umbilical vein endothelial cells (HUVECs). In conclusion, ZSTK474 was demonstrated to have potential in vitro antimetastatic effects on PC3 cells via dual mechanisms: inhibition of metastatic processes including cell migration, invasion and adhesion, and antiangiogenesis via blockade of VEGF secretion. [ABSTRACT FROM AUTHOR]

Four new 28-noroleanane-derived spirocyclic triterpenoids, compounds 1–4, were isolated from the rhizomes of Phlomis umbrosa. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses, in combination with high-resolution MS experiments. [ABSTRACT FROM AUTHOR]

The title compound, C18H16O6·H2O, is a flavonol which was isolated from Cucubalus baccifer (L.). Inter­molecular O—H⋯O and C—H⋯O hydrogen bonds link the mol­ecules to form networks stacked along the a axis. [ABSTRACT FROM AUTHOR]

The title compound, (23 R,24 S)-16b,23:16a,24-diep­oxy-15a,25-dihydr­oxy-9,19-cyclo­lanostane-3- O-β-d-xylopyran­oside methanol solvate, C35H56O9·CH4O, is a cyclo­artane triterpene glycoside which was isolated from the rhizomes of Actaea asiatica. The mol­ecule contains five six-membered rings, two five-membered rings and a three-membered ring. The crystal structure is stabilized by intra- and inter­molecular O—H⋯O hydrogen bonds. [ABSTRACT FROM AUTHOR]

The title compound, a novel triterpenoid, C30H48O4·CH4O, was isolated from the rhizome of Astilbe chinensis (Maxim.) Franch. et Sav. It contains five fused six-membered rings, which adopt half-chair conformations. In the crystal structure, intermolecular O—H...O hydrogen bonds link the molecules, forming an extensive network, which may be effective in the stabilization of the structure. [ABSTRACT FROM AUTHOR]

A new nortriterpenoid, C29H48O6, with a novel skeleton was isolated from the rhizome of Phlomis umbrosa. The compound is composed of a linear array of four fused six-membered rings and a five-membered ring. The central ring has a slightly distorted half-chair conformation, while the other three six-membered rings adopt chair conformations. There are one intra- and four inter­molecular hydrogen bonds, forming an extensive hydrogen-bonding network within the crystal structure. [ABSTRACT FROM AUTHOR]